The long-term goal of this research program is to define the structure, metabolism, and function of proteoglycans as they occur in normal and diseased connective tissue. The research proposal emphasizes studies designed to elucidate the underlying biochemical processes associated with the endocytosis of lysosomal enzymes (testicular beta-galactosidase and liver beta-glucuronidase) and proteoglycans (chondroitin sulfate-keratan sulfate proteoglycan complex), and their packaging by normal and mutant fibroblasts. Attempts will be made to isolate and characterize the recognition markers contained on the assimilated compounded, and to characterize the specific receptor sites contained on the cell membrane. In addition, we propose to continue related studies concerned with the biosynthesis and degradation of cornea keratan sulfate. These studies will include 1) examination of the participation of lipid-phospho-oligosaccharides in the biosynthesis of the carbohydrate chains, and 2) examination of glycosidases involved in the catabolism of keratan sulfate in liver and chondrocytes as a function of age.